Human Disease

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Routes of Transmission

West Nile virus (WNV) is transmitted to humans primarily through the bite of infected mosquitoes (Campbell et al. 2002). However, person-to-person transmission can occur through transfusion of infected blood products or solid organ transplantation (Pealer et al. 2003, Iwamoto et al. 2003). Intrauterine transmission and probable transmission via human milk also have been described but appear to be uncommon (O’Leary et al. 2006, Hinckley et al. 2007). Percutaneous infection and aerosol infection have occurred in laboratory workers, and an outbreak of WNV infection among turkey handlers also raised the possibility of aerosol transmission (CDC 2002, CDC 2003a).

Since 2003, the U.S. blood supply has been routinely screened for WNV RNA; as a result, transfusion associated WNV infection is rare (CDC 2003b). The U.S. Food and Drug Administration (FDA) recommends that blood collection agencies perform WNV nucleic acid amplification test (NAAT) year-round on all blood donations, either in minipools of six or 16 donations (depending on test specifications) or as individual donations. Organ and tissue donors are not routinely screened for WNV infection though a few collection agencies have incorporated screening of donors (Nett et al. 2012, Theodoropoulos et al. 2021).

Clinical Presentation and Evaluation

An estimated 70-80% of human WNV infections are subclinical or asymptomatic (Mostashari et al. 2001, Zou et al. 2010). Most symptomatic persons experience an acute systemic febrile illness that often includes headache, myalgia, or arthralgia; gastrointestinal symptoms and a transient maculopapular rash also are commonly reported (Watson et al. 2004, Hayes et al. 2005, Zou et al. 2010). Less than 1% of infected persons develop neuroinvasive disease, which typically manifests as meningitis, encephalitis, or acute flaccid paralysis (Hayes et al. 2005). WNV meningitis is clinically indistinguishable from aseptic meningitis due to most other viruses (Sejvar and Marfin 2006). Patients with WNV encephalitis usually present with seizures, mental status changes, focal neurologic deficits, or movement disorders (Sejvar and Marfin 2006). WNV acute flaccid paralysis is often clinically and pathologically identical to poliovirus-associated poliomyelitis, with damage of anterior horn cells, and may progress to respiratory paralysis requiring mechanical ventilation (Sejvar and Marfin 2006). WNV-associated Guillain-Barré syndrome has also been reported and can be distinguished from WNV poliomyelitis by clinical manifestations and electrophysiologic testing (Sejvar and Marfin 2006). Cardiac dysrhythmias, myocarditis, rhabdomyolysis, optic neuritis, uveitis, chorioretinitis, orchitis, pancreatitis, and hepatitis have been described rarely with WNV infection (Hayes et al. 2005).

Although people of all age groups appear to be equally susceptible to WNV infection, the incidence of neuroinvasive WNV disease increases with age (McDonald et al. 2021). In addition, among patients with neuroinvasive WNV disease, older adults are more likely to develop encephalitis or meningoencephalitis and have substantially higher case-fatality rates compared with children or younger adults. Solid organ transplant recipients also are at significantly higher risk of severe illness. Severe WNV disease has been described in persons with malignancies, but the relative risk from these or other immunocompromising conditions remains unclear. Hypertension, cerebrovascular disease, chronic renal disease, alcohol abuse, and diabetes mellitus also have been identified as possible risk factors for severe WNV disease, but further research is warranted (Murray et al 2006, Lindsey et al 2012).

The differential diagnosis of arboviral central nervous system disease is broad and includes many infectious (e.g., viral, bacterial, mycoplasmal, protozoal, or mycotic) and noninfectious (e.g., toxic, metabolic, or postinfectious) causes. Other viral causes of acute neurological illness include herpes simplex, enterovirus, rabies, measles, mumps, Epstein-Barr, varicella zoster, and influenza viruses.


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